JSI-124特异性阻断STAT3通路抑制非小细胞肺癌细胞H1975增殖的研究

Targeted blockage of STAT3 pathway with JSI-124 inhibits the proliferation of H1975 cells of non-small-cell lung cancer

目的探讨JSI-124(Cucurbitacin-I,葫芦素)特异性阻断信号转录传导子与激活子3(STAT3)信号通路,抑制非小细胞肺癌(NSCLC)细胞增殖的效应机制。方法以0、0.08、0.16、0.32、0.64、1.25、2.5、5、10μmol/L和0、0.5、1、3、10μmol/L的JSI-124处理人H1975细胞后,CCK-8法、流式细胞仪分别检测细胞增殖和凋亡的相关情况、Western blot法检测被处理细胞中STAT3及其相关蛋白的活化情况、RT-PCR法检测STAT3及相关基因mRNA水平的表达。结果 JSI-124可抑制H1975细胞的增殖,并具有时间及剂量依赖性;JSI-124处理细胞后,STAT3的活化水平显著降低(P<0.05);同时H1975细胞随JSI-124浓度的增加,细胞凋亡水平也逐渐上升。结论 STAT3特异性抑制剂JSI-124可显著抑制NSCLC细胞H1975的增殖并诱导其凋亡。

Objective To explore the effect of inhibition of STAT3 with JSI-124 on the proliferation of non-small-cell lung cancer H1975 cells.Methods CCK-8 assay and flow cytometry were used to detect the inhibitory rate and apoptosis of H1975 after treatment with JSI-124.After using STAT3-specific inhibitor JSI-124,the levels of STAT3 and p-STAT3 protein were determined by Western blot and the levels of STAT3 mRNA were determined by RT-PCR in H1975.Results JSI-124 can inhibit cell proliferation in time and dose dependent manner in the H1975 cells,and enhanced the cell apoptosis(P<0.05).JSI-124 decreased p-STAT3 protein expression,but did not change STAT3 protein expression.Conclusions JSI-124 as a STAT3-specific inhibitor,suppresses the proliferation and enhance apoptosis of H1975 cells.